TY - JOUR
T1 - Serologic Biomarkers of Progression Toward Diagnosis of Rheumatoid Arthritis in Active Component Military Personnel
AU - Loza, Matthew J.
AU - Nagpal, Sunil
AU - Cole, Suzanne
AU - Laird, Renee M.
AU - Alcala, Ashley
AU - Rao, Navin L.
AU - Riddle, Mark S.
AU - Porter, Chad K.
N1 - Funding Information:
Janssen Research and Development had a role in the study design and in the collection, analysis, and interpretation of the data, the writing of the manuscript, and the decision to submit the manuscript for publication. Publication of this article was contingent upon approval by Janssen.
Funding Information:
Supported by Janssen Research and Development, LLC, under a Cooperative Research and Development Agreement (NMR 9245). This article is the result of work supported with resources and the use of facilities at the VA Sierra Nevada Health Care System.
Publisher Copyright:
© 2022 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
PY - 2022/11
Y1 - 2022/11
N2 - Objective: To identify a panel of serum biomarkers that could specifically identify imminent cases of rheumatoid arthritis (RA) before diagnosis. Methods: Serum samples were collected at 4 time points from active component US military personnel, including 157 anti–citrullinated protein antibody (ACPA)–seropositive and 50 ACPA-seronegative RA subjects, 100 reactive arthritis (ReA) subjects, and 76 healthy controls. The cohorts were split into 2 phases, with samples tested on independent proteomic platforms for each phase. Classification models of RA diagnosis based on samples obtained within 6 months prior to diagnosis were developed both in univariate analyses and by multivariate random forest modeling of training sample sets and testing sample sets from each phase. Results: Increases in serum analytes, including C-reactive protein levels, serum amyloid A, and soluble programmed cell death 1 (PD-1), were observed in seropositive RA subjects at the time point closest to diagnosis, up to several years before diagnosis. Only a small fraction of RA subjects had levels above the 95th percentile of healthy control levels until the time period within 6 months of diagnosis. For classification of RA diagnosis using samples obtained within 6 months prior to diagnosis, soluble PD-1 provided superior specificity compared to ReA cases (>89%), with a sensitivity of 48% for RA classification. An 8-analyte model provided superior sensitivity (69%), with comparable specificity relative to ReA (>82%). Conclusion: Our findings demonstrate that imminent RA diagnosis could be classified with high specificity, relative to healthy controls and ReA cases, using a panel of cytokines measured in serum samples collected within 6 months before actual diagnosis.
AB - Objective: To identify a panel of serum biomarkers that could specifically identify imminent cases of rheumatoid arthritis (RA) before diagnosis. Methods: Serum samples were collected at 4 time points from active component US military personnel, including 157 anti–citrullinated protein antibody (ACPA)–seropositive and 50 ACPA-seronegative RA subjects, 100 reactive arthritis (ReA) subjects, and 76 healthy controls. The cohorts were split into 2 phases, with samples tested on independent proteomic platforms for each phase. Classification models of RA diagnosis based on samples obtained within 6 months prior to diagnosis were developed both in univariate analyses and by multivariate random forest modeling of training sample sets and testing sample sets from each phase. Results: Increases in serum analytes, including C-reactive protein levels, serum amyloid A, and soluble programmed cell death 1 (PD-1), were observed in seropositive RA subjects at the time point closest to diagnosis, up to several years before diagnosis. Only a small fraction of RA subjects had levels above the 95th percentile of healthy control levels until the time period within 6 months of diagnosis. For classification of RA diagnosis using samples obtained within 6 months prior to diagnosis, soluble PD-1 provided superior specificity compared to ReA cases (>89%), with a sensitivity of 48% for RA classification. An 8-analyte model provided superior sensitivity (69%), with comparable specificity relative to ReA (>82%). Conclusion: Our findings demonstrate that imminent RA diagnosis could be classified with high specificity, relative to healthy controls and ReA cases, using a panel of cytokines measured in serum samples collected within 6 months before actual diagnosis.
UR - http://www.scopus.com/inward/record.url?scp=85139397238&partnerID=8YFLogxK
U2 - 10.1002/art.42260
DO - 10.1002/art.42260
M3 - Article
C2 - 35671369
AN - SCOPUS:85139397238
SN - 2326-5191
VL - 74
SP - 1766
EP - 1775
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 11
ER -